Paxlovid

Each pink FC tab Nirmatrelvir 150 mg, each white to off-white FC tab Ritonavir 100 mg

COVID-19 patients w/ ≥18 yr not requiring supplemental O₂ & at high risk for progression to severe COVID-19.

300 mg/150 mg bid for 5 days given after +ve results of direct SARS-CoV-2 viral testing & w/in 5 days of onset of symptoms. Moderate renal impairment Reduce dose to 150 mg/100 mg bid for 5 days.

May be taken with or without food: Swallow whole, do not chew/break/crush.

Patients w/ history of clinically significant hypersensitivity. Medicinal products that are highly dependent on CYP3A & potent CYP3A inducers. Severe hepatic & renal impairment.

Not to be taken >5 consecutive days. Not to be used before or after exposure for the purpose of COVID-19 prevention. Not to be used in another indication that is not for COVID-19 treatment. Risk of serious adverse reactions due to interactions w/ other medicinal products. Risk of HIV-1 developing resistance to HIV PIs in individuals w/ uncontrolled or undiagnosed HIV-1 infection. Patients w/ pre-existing liver diseases, liver enzyme abnormalities or hepatitis. Galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. May increase or decrease conc w/ CYP3A inhibitor or inducer medicinal products. Not recommended in patients w/ severe renal impairment (eGFR <30 mL/min) or renal failure. Women of childbearing potential should avoid becoming pregnant during treatment. Patients using combined hormonal contraceptives should use effective alternative contraceptive method or additional barrier method of contraception during treatment & until after 1 complete menstrual cycle after stopping of treatment. Not recommended during pregnancy & in women of childbearing potential not using effective contraception. Discontinue breastfeeding during treatment & for 7 days after last dose of treatment. Ped patient <18 yr.

Dysgeusia; diarrhoea; vomiting.

Decreased exposure w/ apalutamide; carbamazepine; rifampicin. Nirmatrelvir: May induce CYP3A4, CYP2B6, CYP2C8, CYP2C9 (w/ low potential to inhibit BCRP, MATE2K, OAT1, OAT3, OATP1B3 & OCT2) & inhibit MDR1, MATE1, OCT1 & OATP1B1 at clinically relevant conc. Ritonavir: Increased plasma conc of alfuzosin; norpethidine, piroxicam & propoxyphene; fentanyl; loratadine; itraconazole, erythromycin; clozapine or pimozide; salmeterol; Ca channel antagonists (eg, amlodipine, diltiazem, nifedipine); ergot derivatives (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine); HMG CoA reductase inhibitors (eg, lovastatin, simvastatin, atorvastatin, fluvastatin, pravastatin, rosuvastatin); cyclosporine, tacrolimus, everolimus. Increased exposure of lomitapide; clonazepam, diazepam, estazolam, flurazepam, oral & parenteral midazolam, triazolam, buspirone; dexamethasone; both fusidic acid & ritonavir. Increased conc of amphetamine & its derivatives; ranolazine; amiodarone, dronedarone, flecainide, propafenone, quinidine; imipramine, amitriptyline, nortriptyline, fluoxetine, paroxetine, or sertraline; colchicine; fexofenadine; haloperidol, risperidone & thioridazine; lurasidone; quetiapine. Increased plasma levels of buprenorphine & its active metabolites. May increase methadone dose. May decrease morphine levels. Modification of P-gp mediated digoxin efflux. Increased dose of theophylline. Increased serum conc w/ BCRP & acute P-gp inhibition. Increased serum conc of abemaciclib; ceritinib; dasatinib, nilotinib, vincristine, vinblastine; encorafenib; ibrutinib; neratinib; venetoclax; vorapaxar; riociguat; glecaprevir/pibrentasvir. Increased AUC & C_max of afatinib. Increased fostamatinib metabolite R406 exposure. Potentially increased apixaban & dabigatran conc. Increased plasma levels & pharmacodynamic effects of rivaroxaban. Decreased R-warfarin levels. Decreased plasma conc of anticonvulsants; atovaquone. Decreased serum levels w/ phenytoin. Decreased AUC & C_max of 2-hydroxy metabolite of desipramine. Large increased in rifabutin AUC. Avoid co-administration w/ voriconazole; bedaquiline. Increased incidence of GI & hepatic adverse reactions of ketoconazole. Not to co-administer w/ clarithromycin. Not necessary to alter dose of sulfamethoxazole/trimethoprim during concomitant therapy. Increased serum levels of amprenavir, atazanavir, darunavir; maraviroc. Higher frequency of adverse reactions & lab abnormalities w/ efavirenz. Minor reduction in raltegravir levels. Slightly decreased levels of zidovudine. Increased steady-state of bosentan C_max & AUC. Reduced effectiveness of estradiol-containing contraceptives. Increased exposure of lomitapide. Concomitant use of avanafil, sildenafil, tadalafil, vardenafil; alprazolam. Elevated norpethidine conc. Excessive sedative effects w/ zolpidem. Decreased bupropion levels. Decreased plasma cortisol levels w/ inhaled or intranasal fluticasone propionate; corticosteroids metabolised by CYP3A eg, budesonide & triamcinolone. Increased AUC of metabolite prednisolone. Potential interaction w/ levothyroxine.

Antivirals

J05AE30 - nirmatrelvir and ritonavir ; Belongs to the class of protease inhibitors. Used in the systemic treatment of viral infections.

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